New Vitamin D analogs and changing therapeutic paradigms John Cunningham, Daniel Zehnder  Kidney International  Volume 79, Issue 7, Pages 702-707 (April 2011) DOI: 10.1038/ki.2010.387 Copyright © 2011 International Society of Nephrology Terms and Conditions

Figure 1 Vitamin D receptor (VDR) activation: there is an endogenous vitamin D hormonal system with renal (endocrine) and local tissue (paracrine and autocrine) synthesis of calcitriol. The synthesis of calcitriol relies on vitamin D (25(OH)D) sufficiency. The pharmacological treatment with VDR-activating compounds in clinical setup can be divided into two main groups: the prodrugs needing hydroxylation after intake and the already active compounds. Data suggest that active compounds with side chain modification may have an improved side-effect profile. 1,25(OH)D, 1,25-dihydroxyvitamin D. Kidney International 2011 79, 702-707DOI: (10.1038/ki.2010.387) Copyright © 2011 International Society of Nephrology Terms and Conditions

Figure 2 Transfer of vitamin D compounds to the vitamin D receptor (VDR). The diagram shows different levels where compounds can vary in their transport, storage, or effect. Prodrug or active compound is transferred to site-of-action bound to vitamin D binding protein; a cell surface receptor (in the kidney, megalin) enables the uptake into the cell where the compound binds to intracellular binding protein. Prodrugs can be either activated in the liver (25-hydroxylation) or target tissues (25-hydroxylation, 1-hydroxylation). Active compound binds to the VDR and recruit nuclear proteins to activate the target gene. Catabolism occurs in the target tissue. LDL, low-density lipoprotein. Kidney International 2011 79, 702-707DOI: (10.1038/ki.2010.387) Copyright © 2011 International Society of Nephrology Terms and Conditions